The major objective of this research program is to characterize the alteration in electrophysiological properties occurring with cardiac hypertrophy and whether these changes may be responsible in part for the altered excitation-contraction coupling evident in hypertrophied myocardium. Two models of cardiac hypertrophy are being used; the pressure overload induced hypertrophy produced by partial constriction of the pulmonary artery and the hypertrophy produced secondary to chronic thyrotoxicosis. Two separate, but closely co-ordinated studies are in progress. In the first conventional electrophysiological and mechanical techniques are used to investigate the alteration in electrical and mechanical properties of papillary muscles taken from normal and hypertrophied hearts. The second approach involves more sophisticated voltate clamp experiments utilizing the P-strand preparation. In these experiments the voltage-tension relationship and voltage-current relationship will be analyzed in preparations.